Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE] (RESTORE)

• ClinicalTrials.gov Identifier: NCT04945772
• Recruitment Status: Completed
• First Posted: June 30, 2021
• Last Update Posted: March 22, 2024
• Sponsor: Nanoscope Therapeutics Inc.
• Information provided by (Responsible Party): Nanoscope Therapeutics Inc.

Tracking Information

• First Submitted Date: June 15, 2021
• First Posted Date: June 30, 2021
• Last Update Posted Date: March 22, 2024
• Actual Study Start Date: July 13, 2021
• Actual Primary Completion Date: February 27, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 12, 2024)

Efficacy of a single intravitreal injection of Multi-Characteristic Opsin (MCO-010) as assessed by best corrected visual acuity. [ Time Frame: Week 52 ]

Change from Baseline in the Freiburg Visual Acuity (quantitative LogMAR) score for the study eye at Week 52.

Original Primary Outcome Measures (submitted: June 22, 2021)

• Efficacy of a single intravitreal injection of virally-carried Multi-Characteristic Opsin (vMCO-010) assessed by Y- Mobility Test. [ Time Frame: 52 weeks ]
  Change from Baseline in Y-Mobility Test compared to week 52.
• Type, severity, and incidence of ocular and systemic adverse events (AEs) [ Time Frame: 52 weeks ]
  Type, severity, and incidence of ocular and systemic adverse events (AEs), specifically those related to intravitreal injection of vMCO-010

Current Secondary Outcome Measures (submitted: January 12, 2024)

• Efficacy of MCO-010 as assessed by best corrected visual acuity. [ Time Frame: Week 76 ]
  Change from Baseline in the Freiburg Visual Acuity (quantitative LogMAR) score for the study eye at Week 76.
• Efficacy of MCO-010 as assessed by mobility testing. [ Time Frame: Weeks 16,24,32,52,76,100 ]
  Change from Baseline in Multi-Luminance Y-Mobility Test score. Range: -1 to 5, higher score means better outcome.
• Efficacy of MCO-010 as assessed by mobility testing. [ Time Frame: Weeks 16,24,32,52,76,100 ]
  Proportion of subjects with Multi-Luminance Y-Mobility Test score scores of 2 or more light level improvement from Baseline. Range: 0% to100%, higher score means better outcome.
• Efficacy of MCO-010 as assessed by static shape recognition assay. [ Time Frame: Weeks 16,24,32,52,76,100 ]
  Proportion of subjects with Multi-Luminance Shape Discrimination Test scores of 2 or more light level improvements from Baseline. Range: 0% to 100%, higher score means better outcome.
• Efficacy of MCO-010 as assessed by static shape recognition assay. [ Time Frame: Weeks 16,24,32,52,76,100 ]
  Change from Baseline in Multi-Luminance Shape Discrimination Test score. Range: 0 to 5, higher score means better outcome.
• Efficacy of MCO-010 as assessed on visual field. [ Time Frame: Weeks 16,24,32,52,76,100 ]
  Change from Baseline in Visual Fields measured by Humphrey 30-2 perimetry.

Original Secondary Outcome Measures (submitted: June 22, 2021)

• Effect of vMCO-010 as assessed by static shape recognition assay [ Time Frame: 52 Weeks ]
  Change from baseline compared to Week 52 in the % shape recognition accuracy, measured with Static Shape recognition assay, performed at different light intensities
• Effect of vMCO-010 on determination of optical flow direction [ Time Frame: 52 Weeks ]
  Change from baseline compared to week 52 in accuracy determination of optical flow direction
• Effect of vMCO-010 as assessed by Freiburg Visual Acuity [ Time Frame: 52 Weeks ]
  Change from baseline compared to week 52 in Freiburg Visual Acuity.
• Effect of vMCO-010 on pupillary light reflex [ Time Frame: 52 Weeks ]
  Change from baseline compared to week 52 in the % change in pupil size.
• Effect of vMCO-010 on light sensitivity [ Time Frame: 52 Weeks ]
  Change from baseline compared to week 52 in the Full-field Stimulus Threshold (FST).
• To evaluate the effect of vMCO-010 on visual field [ Time Frame: 52 Weeks ]
  Change from baseline compared to week 52 in visual field measured by perimetry.
• Effect of vMCO-010 on functional vision outcomes [ Time Frame: 52 Weeks ]
  Change from baseline compared to week 52 in activities of daily living using the National Eye Institute Visual Function Questionnaire-25. Each question has several responses scored on a scale from 0 to 5, 0 to 6, or 0 to 10, and the Values are calculated in percentages.
• Pharmacokinetic (PK) impact of vMCO-010 on gene reporter expression [ Time Frame: 52 Weeks ]
  Change from baseline compared to week 52 in PK parameters including the rate of increase of fluorescence intensity of reporter measured by fluorescence funduscopy.

Current Other Pre-specified Outcome Measures (submitted: January 12, 2024)

• Efficacy of MCO-010 as assessed by a composite of functional assessments. [ Time Frame: Week 52 ]
  Proportion of subjects demonstrating a ≥2 unit improvement from Baseline in EITHER the MLYMT OR the MLSDT score at Week 52.
• Safety of MCO-010. [ Time Frame: 100 weeks ]
  Incidences, nature, and severity of ocular and non-ocular treatment emergent adverse events (TEAEs).

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
• Official Title: A Phase 2b Randomized, Double-Masked, Sham-Controlled, Study to Evaluate the Efficacy and Safety of Intravitreal Injection of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
• Brief Summary: The purpose of the study is to evaluate the safety and efficacy of a single intravitreal injection of virally-carried Multi-Characteristic Opsin (MCO-010).
• Detailed Description: This multicenter, randomized, double-masked, sham-controlled, dose-ranging study will evaluate 2 dose levels of MCO-010 in up to 18 subjects with retinitis pigmentosa (9 per dose). An additional nine subjects will receive sham injection. Subjects with a confirmed diagnosis of Advanced Retinitis Pigmentosa (RP) based on clinical examination, dilated fundus examination, and genetic testing will be considered for participation in this study. All subjects will continue to be assessed for 100 weeks following treatment with MCO-010.
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

Following a 1:1:1 block randomization schema, 9 subjects will be enrolled in each MCO-010 treatment group, and 9 subjects will be enrolled in the sham-controlled group.

Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description:

Treatment assignment will be unknown (or masked) to the study participants, the evaluating physician (non-injecting), outcomes assessor, the sponsor and its agents.

Primary Purpose: Treatment

Condition

• Retinitis Pigmentosa
• Retinitis
• Retinal Diseases
• Eye Diseases
• Eye Diseases, Hereditary
• Retinal Dystrophies
• Retinal Degeneration

Intervention

• Biological: Gene Therapy Product-MCO-010
  The MCO-010 is an adeno-associated virus serotype 2-based vector carried multi-characteristic opsin (MCO) gene expression cassette
• Procedure: Sham Injection
  Sham Injection

Study Arms

• Experimental: MCO-010- High Dose
  Participants receive 1.2E11gc/eye of MCO-010
  Intervention: Biological: Gene Therapy Product-MCO-010
• Experimental: MCO-010- Low Dose
  Participants receive 0.9E11gc/eye of MCO-010
  Intervention: Biological: Gene Therapy Product-MCO-010
• Sham Comparator: Sham Injection
  Participants receive sham injection
  Intervention: Procedure: Sham Injection

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 22, 2021): 27
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: January 18, 2024
• Actual Primary Completion Date: February 27, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Age ≥ 18 years
2. Able to comprehend and give informed consent.
3. Confirmed diagnosis of Advanced Retinitis Pigmentosa (RP) based on clinical examination, dilated fundus examination, and genetic testing.
4. Best-Corrected (Freiburg) Visual Acuity worse than 1.9 LogMAR (Snellen equivalent 20/1600) in the study eye and no better than 1.6 LogMAR (Snellen equivalent 20/800) in the fellow eye during screening.

Exclusion Criteria:

Subjects are excluded from the study if any of the following criteria apply:

1. Prior participation in gene therapy program
2. Pre-existing conditions in the study eye such as glaucoma, diseases affecting the optic nerve causing significant visual field loss, active uveitis, corneal or lenticular opacities).
3. Presence of any complicating systemic diseases such as malignancies whose treatment could affect central nervous system function.
4. Active ocular inflammation or recurrent history of idiopathic or autoimmune associated uveitis.
5. Having received retinal prothesis (such as ARGUS-II) or any gene or stem cell therapy (ocular or non-ocular).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Puerto Rico, United States

Administrative Information

• NCT Number: NCT04945772
• Other Study ID Numbers: NTXMCO-002.
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: The results of the clinical trial will be made available when the study is completed. The results will be published on this site and be available to conference presentations and publications.
• Time Frame: 12 months after the study is completed
• Access Criteria: Efficacy and Safety Results

• Current Responsible Party: Nanoscope Therapeutics Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Nanoscope Therapeutics Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Dr Samarendra Mohanty; Nanoscope Therapeutics Inc.

• PRS Account: Nanoscope Therapeutics Inc.
• Verification Date: March 2024